This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Since neither an effective vaccine or microbicide to prevent HIV transmission exist, we are currently examining combination strategies to see synergy exists between these approaches. Initial studies using the gp41-targeted fusion inhibitor peptide T-1249 as the microbicide arm, with an rAd26 prime, rAd5HVR48 boost as the vaccine arm and SIVmac251 as the vaginal challenge virus ("high-dose", progesterone-treated macaque model) demonstrated better protection in the combination arm than vaccine or microbicide arms alone. We have however since performed a second study using CMPD167 and the ad5 vaccine and challenged animals vaginally with SIVmac251 and did not see a significant difference. In fact the study was confounded by the fact that 3/8 control animals did not get infected but this result also made us check the susceptibilities of CMPD167 and other fusion inhibitors and we discovered there is a log difference in susceptibility of SIVmac to CCR5 fusion inhibitors compared to the SHIV162P3/4 we have used in prior studies. We are now repeating this experiment using maraviroc, and will challenge with SHIV162P3 to overcome this obstacle while continuing to investigate the differences in susceptibility of SIV and SHIV.